In vivo optical molecular imaging involves the use of light emitting tracers combined with sophisticated sensing modalities to perform in vivo imaging of genetic and molecular information. In contrast to the classical diagnostic imaging tools which image the end effects of the diseases, optical molecular imaging could enhance our knowledge of biological phenomena, monitor genetic expression and the alteration of cells, and lead to earlier detection of diseases. With the development of exotic molecular probes with easily detectable bioluminescence and fluorescence labels, optical molecular imaging has emerged as an important new field within biomedical imaging. This paper reviews this state-of-the-art imaging technology and signal processing issues to monitor molecular and cellular events in living organisms.